Zirconium oxide and zirconium nitride coated stents

ABSTRACT

Stents fabricated from a substrate of a low modulus metal coated with blue to black zirconium oxide or zirconium nitride. The coating provides enhanced thrombogenicity, biocompatibility, blood compatibility, corrosion-resistance, friction and microfretting resistance, durability, and electrical insulation, where applicable. The coatings may be applied to low modulus metallic substrates by physical or chemical vapor deposition as well as other ion-beam assisted methods. Preferably, however, for optimizing attachment strength, the stents are fabricated from zirconium or zirconium-containing alloys and the coatings are formed by oxidizing or nitriding through an in situ method that develops a coating from and on the metal surface of the stent, without need for depositing a coating on the metal surface.

RELATED APPLICATIONS

This is a division of application Ser. No. 08/112,587, filed on Aug. 26, 1993, which is a continuation-in-part of U.S. Ser. No. 07/919,932, filed Jul. 27, 1992, now U.S. Pat. No. 5,282,850, which is in turn a continuation-in-part of U.S. Ser. No. 07/830,720, filed on Feb. 4, 1992, issued as U.S. Pat. No. 5,258,022, which is a continuation-in-part of Ser. No. 07/557,173, filed on Jul. 23, 1990, issued as U.S. Pat. No. 5,152,794, which is in turn a continuation-in-part of U.S. Ser. No. 07/385,285, filed on Jul. 25, 1989, issued as U.S. Pat. No. 5,037,438.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The invention is of stents of enhanced biocompatibility, blood compatibility, and corrosion resistance, as well as superior low friction, flexibility, and corrosion characteristics. More specifically, the stents are fabricated from relatively low modulus metals, such as zirconium or a zirconium-containing alloy, and are coated with blue to black zirconium oxide or zirconium nitride to provide enhanced blood compatibility, microfretting resistance, electrical insulation, and corrosion resistance where applicable.

2. Description of the Related Art

With advances in the technology for treating heart diseases, there has developed an increasing demand for sophisticated cardiovascular implants and surgical tools for use in cardiovascular surgery.

It is currently known to use balloon-expandable stents to prop open blood vessels that have become damaged so that they are prone to collapse, or blood vessels that have become coated on the inside with plaque, thereby impeding the flow of blood. Typically, these stents are inserted by means of a guide wire with a stent in a collapsed state at its distal end. Once the stent is in position, a balloon positioned inside the stent is inflated so that the stent expands and props open the desired area of the blood vessel. Such stents are also used for gastrointestinal, urinary, and other non-cardiovascular applications.

SUMMARY OF THE INVENTION

The invention provides improved stents fabricated from a low modulus metallic material, such as zirconium and zirconium-containing alloys, covered with a biocompatible, microfretting and corrosion-resistant, hemocompatible, electrically insulative coating of blue to black zirconium oxide or yellow to orange zirconium nitride. These coatings are tightly adherent to the underlying metal and are of a sufficient thickness to provide the desired electrical insulation, blood compatibility, microfretting resistance, and corrosion resistance, as may be required for the particular stents.

In one embodiment, the invention provides balloon-expandable stents fabricated from low modulus metals coated with blue to black zirconium oxide or zirconium nitride. These stents are generally used temporarily or permanently to prop open tubular conduits with the body, such as blood vessels, urinary tract, gastrointestinal tract, and the like. The stents may be positioned within a blood vessel, for example, using conventional balloon-expanding tools, and may then be expanded into position to prop open the walls of the blood vessel. The blue to black zirconium oxide or yellow to orange zirconium nitride coatings provide highly hemocompatible and biocompatible surfaces in contact with blood vessel walls and blood thereby minimizing adverse blood reaction and build up of thrombus or other adverse blood components on the stent. Thus, the invention coated stent reduces the likelihood of thrombus build up on its surface which might subsequently require further surgery to clear any developing blockage. The stents of the invention also provide corrosion resistance which is an important consideration, particularly for gastrointestinal and urinary applications.

Furthermore, the oxide- or nitride-coated surfaces according to the invention may be coated with other compositions to further enhance biocompatibility and performance. For example, phosphatadyl choline, heparin, proteins, or other surface treatment may be applied for reducing platelet adhesion or other adverse cellular or tissue response to surfaces in contact with blood, or boronated or silver-doped hardened surface layers to reduce friction and wear if the implant is subject to microfretting or other mechanical wear. In certain instances, it may be desirable to coat the surfaces according to the invention with a medicament such as an antibiotic, anticoagulant, and the like, as needed for the particular application.

The thickness of the hard zirconium oxide or nitride coating is preferably less than about 5 microns (i.e., in the range about 3 to about 6 microns) for optimal residual compressive stresses and minimal dimensional changes or distortion during oxidation or nitridation. However, the thickness of the coating is frequently not critical, for instance where the surface coating provides enhanced hemocompatibility and biocompatibility and is not subject to forces requiring optimal residual compressive stresses. Thus, in these cases, the thickness of the coating is limited only by its own integrity, i.e., that it is not subject to cracking and spalling, thereby potentially releasing particulates into the body of the patient. Such coatings may range from about 0.1 to about 20 microns or more in thickness.

BRIEF DESCRIPTION OF THE DRAWINGS

A better understanding of the present invention can be obtained when the following detailed description of the preferred embodiment is considered in conjunction with the following drawings, in which:

FIG. 1 is a schematic diagram showing a balloon expandable stent, according to the invention, positioned within a segment of a blood vessel to be propped open.

FIG. 2 is a schematic diagram showing a balloon expanding a stent into position within a blood vessel.

FIG. 3 is a schematic diagram of a stent, according to the invention, in place in a blood vessel.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The invention provides low modulus metallic stents coated with a layer of blue to black zirconium oxide or zirconium nitride. These coatings provide a blood compatible, microfretting resistant, electrically insulative, stable, and corrosion resistant ceramic coating. Furthermore, these ceramic blue to black zirconium oxide or zirconium nitride coatings may be further overlaid with a thin coating of phosphatadyl choline, heparin, or other surface treatment for further reducing platelet adhesion, if the stents will be in contact with blood. Other medicaments may also be coated onto the ceramic surfaces of the invention. The ceramic coatings of the invention may also be modified by boronation or silver doping to further improve friction and wear characteristics, if necessary.

The term "low modulus" as used to describe the metallic compositions preferred in this invention include those metallic compositions that preferably have a modulus of elasticity less than about 130 GPa.

The term "blue to black" as used to describe zirconium oxide means that the color of the oxide may range from blue to black, depending on zirconium concentration in the oxidized alloy or process conditions that produce the coating. Thus, for pure zirconium, the blue to black oxide formed by the preferred in situ process is substantially monoclinic zirconium oxide. However, if a zirconium alloy is used, then, for the useful zirconium alloys, the in situ process will produce a surface containing a mixture of oxides, but still substantially zirconium oxide, to produce the blue to black appearance. If an ion beam deposition assisted or other non-in situ process is used, such as chemical or vapor deposition, then the color of the oxide is not affected by the substrate metal. In this case, the white tetragonal or cubic ZrO₂ is possible as well. Such coatings are useful as "overlay" coatings on an in situ blue-black zirconium oxide or yellow-orange zirconium nitride coating. Since the hardness match between such overlays and the in situ coatings are closer than between overlay and substrate metal, the coatings are more firmly attached and have superior integrity. Other hard coatings are also useful as overlays--such as amorphous diamond-like carbon coatings, wear-resistant coatings formed by silver deposition, and lubricious boronated coatings.

The term "yellow to orange" as applied to zirconium nitride refers to the range of colors of zirconium nitride and the comments above about alloys and consequent mixtures of oxides with zirconium oxide also apply in the nitride context.

Further characteristics and properties of the zirconium oxide and zirconium nitride coatings are described in U.S. patent application Ser. No. 08/112,587, filed Aug. 26, 1993, which is hereby incorporated by reference.

FIG. 1 shows an expandable stent 20, in non-expanded state, positioned on the distal end of a balloon expandable segment 22 of a guide wire 24. The stent is fabricated from a low modulus metal, such as zirconium or zirconium-containing alloy, and is fabricated so that it can be collapsed over a balloon segment of a balloon catheter. When the stent is in position, within a tubular conduit in the body such as a segment of blood vessel, for example, to be propped open, the balloon is expanded, as shown in FIG. 2, thereby expanding the stent radially outward up to the blood vessel wall 26 so that means for gripping soft tissue, such as barbs (not shown), on the outer surface of the stent engage and grip blood vessel tissue to anchor the stent in position. In this way, the blood vessel is permanently propped open as shown in FIG. 3. The invention blue to black zirconium oxide or yellow to orange zirconium nitride coatings provide a blood compatible low friction surface to which platelets and other adverse blood-borne compositions will not tend to adhere thereby preventing build up of adverse tissue and subsequent blockage of the propped open blood vessel. Again, the thickness of the coating may range from about 0.1 to about 20 microns, preferably about 1 to about 10 microns, most preferably about 3-6 microns.

While the oxide and nitride coatings of the invention can be applied by various coating methods, in situ coating is preferred. These in situ methods require that the metal composition be zirconium or its alloys so that the coating can be formed by oxidizing or nitriding the metal itself, not by depositing zirconium oxide or nitride on the metallic surface by coating deposition methods. Thus, the in situ methods include oxidation or nitridation in air, oxygen (oxidation), nitrogen (nitridation), and salt baths. These methods are described below.

In order to form continuous and useful zirconium oxide or nitride coatings over the surface of zirconium alloys by an in situ method, the alloy should contain from about 50 to about 100 wt. % zirconium, preferably 80 to 100 wt. %. Common alloying elements include niobium, tantalum, and titanium, with often times the presence of hafnium. Yttrium may also be alloyed with the zirconium to enhance the formation of a tougher, yttria-stabilized zirconium oxide coating during the oxidation of the alloy. During oxidation, the protective surface layer will contain various amounts of zirconium oxide depending on the alloy composition. The greater the level of zirconium oxide, the darker (tending to black) the ceramic oxide appearance. However, this appearance may be blue for alloys with relatively lower levels of zirconium or for thinner oxide layers. For ZrO₂ surface oxides, the monoclinic structure is stable at room temperature and is black in appearance. However, higher temperature oxide structures such as cubic or tetragonal can range from grey to white. While zirconium and zirconium alloys may be custom-formulated by conventional methods known in the art of metallurgy, a number of suitable alloys are commercially available. These commercial alloys include among others Zircadyne 705, Zircadyne 702, and Zircalloy, Ti-Zr and Ti-MO-Zr alloys. Ti-Nb-Zr alloys are disclosed in U.S. Pat. No. 5,169,597, entitled "Biocompatible Low Modulus Titanium Alloy for Medical Implants" (hereby fully incorporated by reference) and are the preferred low modulus metals. It should be understood that other low modulus metallic compositions not containing zirconium may also be used if the coating is applied by other than in situ methods, e.g., chemical vapor deposition, physical vapor deposition.

To fabricate the coated article by an in situ process, the appropriate substrate is first produced and then subjected to process conditions which cause the natural (in situ) formation of a tightly adhered, diffusion-bonded coating of essentially zirconium oxide on its surface. The process conditions include, for instance, oxygen-containing gas, steam, or water oxidation or oxidation in a fluidized or salt bath. These processes ideally provide a dense, blue to black, hard, low-friction, wear-resistant zirconium oxide film or coating of thicknesses typically less than several microns (10⁻⁶ meters) on the surface of the prosthesis substrate. In some instances, the zirconium-containing oxide coating can be as thin as 0.1-0.2 microns and still provide useful protection. Typically, below this coating, there is a zone wherein diffused oxygen from the oxidation process increases the hardness and strength of the underlying substrate metal, and optimizes coating durability and attachment strength.

Unlike the prior art titanium oxides of, for example, Steinemann's U.S. Pat. No. 3,643,648, in the preferred in situ oxidation method the oxygen supplied to form the blue, blue to black, zirconium oxide coatings of the invention is also a beneficial alloying component which improves the immediate substrate metal hardness, which in turn improves oxide attachment strength and durability and also improves the base-metal strength. Thus, the fatigue strength of the underlying zirconium metal is improved, thereby increasing the potential life of the stent. In contrast, oxidation of titanium alloys tends to form multiple oxides of titanium, which are less well attached to the metal substrate, and importantly, stabilizes the lower strength α-phase which significantly reduces the metal's fatigue strength.

The air, oxygen, steam, and water oxidation processes are described in now-expired U.S. Pat. No. 2,987,352 to Watson, the teachings of which are incorporated by reference as though fully set forth. The air oxidation process provides a firmly adherent black, blue-black, or blue layer of essentially zirconium oxide (ZrO₂) of mainly monoclinic crystalline form, depending upon specific conditions of oxygen and water vapor levels during the process. If the oxidation process is continued to excess, the coating will whiten and tend to separate from the metal substrate. An in situ oxidation step may be conducted in either oxygen, air, steam, hot water, salt baths or fluidized beds. For convenience, the metal prosthesis substrate may be placed in a furnace having an oxygen-containing atmosphere (such as air) and typically heated at 700°-1100° F. up to about 6 hours. However, other combinations of temperature and time are possible. When higher temperatures are employed, the oxidation time should be reduced to avoid the formation of the a less-adherent oxide.

It is preferred that a blue-black zirconium oxide layer ranging in thickness from less than one micron up to about 6 microns should be formed, although thicker coatings ranging from about 1 to about 20 microns are also useful. For example, furnace air oxidation at 1000° F. for 3 hours will form an oxide coating on Zircadyne 705 about 3-4 microns thick. Longer oxidation times and higher oxidation temperatures will increase this thickness, but may compromise coating integrity if thickness exceeds about 20 microns. For example, one hour at 1300° F. will form an oxide coating about 14 microns in thickness, while 21 hours at 1000° F. will form an oxide coating thickness of about 7 to about 9 microns. Of course, because only a thin oxide is necessary on the surface, only very small dimensional changes, typically less than 10 microns over the thickness of the stent, will result. In general, thinner coatings (up to about 6 microns) have better attachment strength, and more favorable residual surface stresses.

One of the salt-bath methods, also considered in situ methods, that may be used to apply the zirconium oxide coatings to the metal alloy stent, is the method of U.S. Pat. No. 4,671,824 to Haygarth, the teachings of which are incorporated by reference as though fully set forth. The salt-bath method provides a similar, slightly more abrasion resistant blue to black zirconium oxide coating. The method requires the presence of an oxidation compound capable of oxidizing zirconium in a molten salt bath. The molten salts include chlorides, nitrates, cyanides, and the like. The oxidation compound, sodium carbonate, is present in small quantities, up to about 5 wt. %. The addition of sodium carbonate lowers the melting point of the salt. As in air oxidation, the rate of oxidation is proportional to the temperature of the molten salt bath and the '824 patent prefers the range 550°-800° C. (1022°-1470° C.). However, the lower oxygen levels in the bath produce thinner coatings than for furnace air oxidation at the same time and temperature. A salt bath treatment at 1290° F. for 4 hours produces an oxide coating thickness of roughly 7 microns. Residual contaminants in the salt bath may be inadvertently left on the treated implant surface and produce adverse clinical results. While some of these may be removed by polishing and washing, it is nonetheless preferred to use the gas (air) oxidation/nitridation processes which provides less possibility of contamination by other elements.

Whether air oxidation in a furnace, in a fluidized bed, or salt bath oxidation is used, the zirconium oxide coatings are quite similar in hardness. For example, if the surface of a wrought Zircadyne 705 (Zr, 2-3 wt. % Nb) stent substrate is oxidized, the hardness of the surface shows a dramatic increase over the 200 Knoop hardness of the original metal surface. The surface hardens of the blue-black zirconium oxide surface following oxidation by either the salt bath or air oxidation process is approximately 1700-2000 Knoop hardness.

In situ air or oxygen oxidation is the preferred method for producing the invention oxide coatings because it minimizes the potential for surface contamination, and allows oxygen diffusion into the metal substrate thereby allowing the formation of a tightly adherent oxide coating while also strengthening the zirconium or zirconium alloy metal substrate.

While the above discussion has dealt mainly with blue to black zirconium oxide coatings on prostheses, zirconium nitride (yellow-orange) coatings are also effective in reducing wear on opposing surfaces and preventing corrosion of the underlying substrate by body fluids.

Even though air contains about four times as much nitrogen as oxygen, when zirconium or zirconium alloy is heated in air as described above, the oxide coating is formed in thermodynamic preference to the nitride coating. This is because the thermodynamic equilibrium favors oxidation over nitridation under these conditions. Thus, to form an in situ nitride coating the equilibrium must be forced into favoring the nitride reaction. This is readily achieved by elimination of oxygen and using a nitrogen or ammonia atmosphere instead of air or oxygen when a gaseous environment (analogous to "air oxidation") is used.

In order to form an in situ zirconium nitride coating of about 5 microns in thickness, the zirconium or zirconium alloy stent should be heated to about 800° C. for about one hour in a nitrogen atmosphere. Thus, apart from the removal of oxygen (or the appropriate reduction in oxygen partial pressure), or increasing the temperature, conditions for forming the zirconium nitride coating do not differ significantly from those needed to form the blue to black zirconium oxide coating. Any needed adjustment would be readily apparent to one of ordinary skill in the art.

When a salt bath method is used to produce an in situ nitride coating, then the oxygen-donor salts should be replaced with nitrogen-donor salts, such as, for instance, cyanide salts. Upon such substitution, a nitride coating may be obtained under similar conditions to those needed for obtaining an oxide coating. Such modifications as are necessary may be readily determined by those of ordinary skill in the art.

Alternatively, the zirconium oxide or nitride may be deposited onto the zirconium or zirconium alloy surface via other techniques than the in situ gaseous and salt bath methods described above. These methods encompass, for example, standard physical or chemical vapor deposition methods, including those using an ion-assisted deposition method. Techniques for producing such an environment are known in the art.

As in the case of the zirconium oxide coatings, the nitride coatings are useful even at thicknesses as low about 0.1 micron. However, thicknesses from about 1 to about 20 microns are preferred and the range about 3 to about 6 microns is most preferred.

If desirable in the particular application, the zirconium oxide or nitride coated stent may be further coated by silver doping or boronation to improve wear-resistance. Additionally, amorphous diamond-like carbon, or other hard, biocompatible coatings may also be applied to either the base low modulus metal or to the oxidized or nitrided surface layer. When deposited over the hard oxide or nitride surface layer, amorphous diamond-like carbon and other types of hard overlay coatings will have improved attachment strength due to a closer hardness match than that between such coatings and relatively softer metal surfaces.

Although the invention has been described with reference to its preferred embodiments, those of ordinary skill in the art may, upon reading this disclosure, appreciate changes and modifications which may be made and which do not depart from the scope and spirit of the invention as described above and claimed below. 

I claim:
 1. An expandable stent for supporting a tubular conduit of a living body from collapsing inward, the stent comprising:(a) a radially outwardly expandable substantially cylindrical stent body of a low elastic modulus metallic composition for insertion in a tubular conduit of a living body, the stent body having a longitudinal bore therethrough for receiving a means for expanding the body radially outwardly and outer surfaces exposed to body fluid and body tissue when the stent is in use; (b) a corrosion-resistant, biocompatible, hemocompatible, durable, stable coating selected from the group consisting of zirconium oxides, ranging in color from blue to black, and zirconium nitrides, ranging in color from yellow to orange; said coating disposed on surfaces of the stent body exposed to body fluid and body tissue when the stent is in use; and (c) anchoring means for engaging the tubular conduit and anchoring the stent body in a radially outward expanded position thereby supporting the tubular conduit from collapsing inward.
 2. The stent of claim 1, wherein the coating is from about 0.1 to about 20 microns thick.
 3. The stent of claim 1, wherein the stent body comprises a metal selected from the group consisting of zirconium and zirconium-containing alloys.
 4. The stem of claim 3, wherein the stem body further includes a sub-surface zone containing diffused oxygen and the coating comprises diffusion-bonded blue to black zirconium oxides.
 5. The stent of claim 4, wherein the coating is from about 0.1 to about 20 microns thick.
 6. The stent of claim 1, wherein the stent body further comprises a second coating selected from the group consisting of antibiotics and anticoagulants, wherein said second coating is applied over said corrosion-resistant, biocompatible, hemocompatible, durable, stable coating.
 7. The stem of claim 1 further comprising a silver-containing overlay coating over the corrosion-resistant, biocompatible, hemocompatible, durable, stable coating.
 8. The stent of claim 1 further comprising overlay coatings over the coating, said overlay coatings selected from the group consisting of amorphous diamond-like carbon, cubic zirconia, and white tetragonal zirconia.
 9. The stent of claim 1 further comprising a boronated overlay coating over the corrosion-resistant, biocompatible, hemocompatible, durable, stable coating.
 10. The stent of claim 1 wherein the radially outwardly expandable substantially cylindrical stent body of a low elastic modulus metallic composition comprises a wire mesh of a low elastic modulus metallic composition.
 11. The stent of claim 10, wherein the wire mesh further comprises the anchoring means.
 12. The stent of claim 1, wherein the anchoring means are barbs disposed on an outer surface of the stent body. 